PROJECTSUMMARY:ThisExploratoryClinicalTrialsofNovelInterventionsforMentalDisorders(RFA-MH- 16-406)grantapplicationproposesastudyofeffectsinadolescents/youngadultsofanovelpsychobehavioral intervention,BrainEmotionSelf-MonitoringandRegulationTherapy(BE-SMART),designedtotargetbrain circuitryunderlyingimpairedemotionalregulation.Emotionaldysregulationiscommon,causessuffering, disabilityandincreasinglyshowsimportanceinsuicide.Convergingresearch,includingfromourgroup, demonstratesemotionaldysregulationanditsunderlyingbraincircuitryascentralinBipolarDisorder(BD).Yet, previouspsychobehavioraltreatmentshavenottranslatedtheneuroscientificfindingsintotargeted interventions.Itisespeciallypressingtostudytargetingofthiscircuitryduringadolescenceandyoung adulthood,thetypicalperiodoftransitionfromsubsyndromalemotionaldysregulationtoBD,asdatasupport underlyingalteredcircuitrydevelopmentduringthistime.Interventionsthatsteertrajectoriesbackontrack couldimprovesymptomsandprognosis.Moreover,BDprovidesamodeltostudydysregulationinvolving excessivepositive,negativeandmixedemotionalstates.Currenttreatmentsoftenaddressoneemotional state,buttreatmentsdesignedtoaddressbothemotionalextremesareneeded.Datasupportbottom-updaily circadianrhythm(DR),andtop-downexecutivecontrol(ER),mechanismsinregulatingemotions.Pilotstudyof theBE-SMART,whichincludedDRandERcomponents,providedpromisinginitialdataofimprovedemotional brainandbehaviorregulation,includingfindingsthatsuggestDRandERcomponentsbothaffectemotional circuitryandmayaffectdifferentaspectsofcircuitry,behaviorsandsymptoms.However,thesecomponents havenotbeenstudiedseparately.IntheR61phase,wewillseparatelyassessengagementofemotional regulationbraincircuitry(functionalmagneticresonanceimaging)andbehaviorbyDRorERcomponents (N=26withBDpergroup),at6-and12-weekdoses.Ifsuccessfulindemonstratingtargetengagement,wewill useR61datatogenerateanoptimized,revisedBE-SMART-Rversion.IntheR33,wewillperforma preliminaryrandomizedcontrolledtrialofadolescentsandyoungadultswithBDtotestfeasibility,acceptability, signalsofefficacyandassociationsbetweentargetengagementandmoodsymptomimprovementofBE- SMART-R(N=64),comparedtoapsychoeducationalcontrolintervention(N=32).Thiswillbethebasisfor subsequentstudiespoweredtoestablishBE-SMART-Refficacyandinterventionmediatorsandmoderators, producinganeasilydisseminablenewinterventionthatmaybepersonalized.Alongtermgoalistotarget neurodevelopmentaltrajectoriesearlierinthediseasecoursetopreventprogression.Thisstudyhaspotential fortremendousscientificandpublichealthbenefitinrevealingnovelinsightsintobehavioralchangesthat influencebraincircuitrymechanismsinpositiveandnegativevalenceandarousalsystems,anddevelopingBD andtransdiagnosticcircuitry-targetedpsychobehavioralinterventions.